Forged, grey market, and illegal re-imports are of increasing concern in the pharmaceutical industry. This is not only a topic in the third world, where the fraction of counterfeit pharmaceutical products in the supply chain is sometimes above 50%. This problem has now reached the second and first worlds likewise, especially as pharmaceuticals are often much more expensive in these areas. AIDS and cancer drugs are sometimes subsidized in developing countries, which enhances the danger of illegal re-imports.
Anti-counterfeiting strategies currently in use in the pharmaceutical industry have so far not been very successful in preventing forgery, illegal re-imports and other activities commonly summarized as counterfeiting. Anti-counterfeiting features in the pharmaceutical market nowadays are generally only applied to packages. Holograms, optically variable inks, fluorescent dyes, special printing techniques like micro-printing, and other security features are attached to the packages by use of adhesive tags, or these are laminated to the carton, or they are directly applied to the packages. The main drawback of such labels is that they can be removed from the product or the packaging and reused or analyzed. Some companies offer security features applied to the sealing foil of blister packages, but these features possess the same disadvantages.
No secure labeling of the pharmaceutical material itself, e.g., of solid dosage forms such as pills, is in the market yet. Techniques that use forgery-resistant signatures, such as DNA of known sequence (U.S. Pat. No. 5,451,505) or molecules with characteristic isotopic composition or micro-particles with characteristic color layer sequence (U.S. Pat. No. 6,455,157 B1) are not applicable here, as these signatures incorporate biologically active components that are consumed with the pharmaceutical material. Certification authorities, such as the Food and Drug Administration (FDA) in the U.S., have not granted approval for such anti-counterfeiting solutions. Only a few ideas of applying a hologram to edible products have been published. One is based on coating an edible product with a thermo-formable and thus embossable layer (WO 01/10464 A1). As this layer alters the composition of the product, as well as the production process, a new approval of the drug from certification authorities would be needed. Further the heating during the thermo-forming steps can harm many active agents. In another approach a polymer solution is brought into contact with a diffraction relief mold and then hardened upon drying (U.S. Pat. No. 4,668,523). The drying step can be accelerated by heating, and in the end the hardened edible polymer product possesses the diffractive relief of the mold. This method is limited to polymer solutions, it is very slow, and the heating step can be harmful to active agents used in pharmaceutical products, as it may negatively affect the activity of the active pharmaceutical agents.
One significant opportunity in designing pharmaceutical dosage forms is that of product identification and differentiation. It is useful, both from a consumer safety perspective and from a commercial perspective, to have a pharmaceutical dosage form with a unique appearance that is readily recognizable and identifiable.
One currently used technique for providing unique dosage form identification includes the use of intagliations. Intagliations are impressed marks typically achieved by engraving or impressing a graphical representation, for example a figure, mark, character, symbol such as a letter, a name, a logo, a pictoral representation, and the like, or any combination thereof; in a tablet or other solid dosage form, such as by a punching procedure. U.S. Pat. No. 5,827,535, for example, describes soft gelatin capsules with an external surface having defined thereon an impressed graphical representation. U.S. Pat. No. 5,405,642 discloses a method of highlighting intagliations in white or color-coated tablets by spraying onto said tablets a suspension comprising a filling material having a different color, a waxy material and a solvent, then removing the solvent and the excess filling and waxy material. However, it is often difficult to maintain the waxy material in an amount sufficient to promote suitable bonding of the filling material, yet be suitably removable with solvent.
EP 088,556 relates to a method of highlighting intagliations in white or colored tablets by contacting said tablets with a dry, powdery material having a different color than that of the tablet surface, then removing the excess powdery material not deposited in the intagliations. Disadvantageously, it has been found that the adhesion of the powdery material to the intagliations is not satisfactory, as the material shows a tendency to loosen and fall out.
EP 060,023 discloses a method of emphasizing intagliations in colored (i.e., not white) solid articles, in particular tablets, by coating the tablet surface and filling up the intagliations with a coating film comprising an optically anisotropic substance. An optical contrast between the tablet surface and the intagliations is obtained, presumably due to different orientation of the optically anisotropic substance on the tablet surface and in the intagliations. However, this technique is limited to colored articles and only allows for the use of optically anisotropic filling materials.
Labeling fluorescing pharmaceutical products by jetting an inkjet a non fluorescing material onto the UV-fluorescing substrate of the product is known from the EP1640421A1. Printed images are created when an UV light is applied to the product. The fluorescent product fluoresces while the non-UV fluorescent inkjet printed area does not. To visualize the labels UV light is needed.
Another way to identify and differentiate one dosage form from another is via application of microreliefs to the dosage form. See, e.g. U.S. Pat. No. 4,668,523 and WO 01/10464 (microreliefs in the outer surface of dosage form). A microrelief is a regular pattern of ridges and grooves and the like that may display a visual effect or optical information when exposed to suitable light. Disadvantageously, production difficulties could be encountered when using these methods to stamp microrelief patterns into tablets having irregular shapes and/or surfaces.
WO 2006/047695 shows a variety of methods to manufacture pharmaceutical dosage forms showing different kinds of microreliefs embedded into their surface. However, based on further review, it seems that the solutions proposed by WO 2006/047695 result in microreliefs that are not recognizable by the human eye. In particular, overcoating of microstructures usually makes them invisible because most overcoatings have a similar optical index of refraction as the pharmaceutical dosage form completely eliminating optical reflections from the interface between the two.
The use of the moiré effect in security features for object of value is known in the art. E.g. US2007/0177131A1 teaches moiré pattern in a first layer on credit cards, banknotes or identity cards, the pattern being verified by superposing the first layer with a moiré analyzer in a second layer. The first layer with the moiré pattern is disposed on a carrier layer. Both are fixed to the object of value or the package. The first layer can be removed from the object and reused on a different object which is critical especially for identity documents.